The present invention concerns a dressing containing one or more active medicaments for controlled release.
Various bandages or dressings of this type are known, consisting of
(a) A non-adhesive water-tight film, foam or the like arranged on the side of the bandage which is not intended to face the patient's skin. PA1 (b) A layer of an adhesive material consisting of a continuous phase containing an adhesive and e.g. composed of an elastomer, a plasticizer for elastomers, a tackifying resin and optionally an oil-based extender as well as an antioxidant, and optionally one or more water soluble or water swellable hydrocolloids, such as starch or cellulose derivatives or other hydrophilic polymers, as well as medicaments, such as antiseptics, antibiotics and antiinflammatory agents. PA1 (c) A removable release layer. PA1 (a) a physically cross-linked elastomer in the form of polyisobutylene, one or more styrene olefin styrene block copolymers or ethylene propylene block copolymers, and optionally containing one or more of components b-e PA1 (b) a hydrocarbon resin in the form of a polymer or copolymer of cyclopentadiene, dicyclopentadiene, .alpha.-pinene and/or .beta.-pinene, PA1 (c) an antioxidant, PA1 (d) an oil extender consisting of one or more mineral oils, and PA1 (e) an elastomer polar plasticizer, such as e.g. an ester of an polyethylene glycol or polypropylene glycol, or an ester of a di- or polybasic carboxylic acid with a preferably aliphatic alcohol, being particularly preferred.
Such bandages, which are primarily intended for use on wounded skin areas, are known e.g. from EP Patent Applications Nos. 92999 and 122344 as well as from DK Patent No. 154 806.
Other bandages of a similar type, but which are also used for transcutaneous medication, are known from U.S. Pat. No. 4,904,247 and from EP Patent Application No. 186019.
With the exception of the bandage known from DK Patent No. 154 806, it is not possible to control or regulate the release of medicament from the bandages mentioned above.
Thus, in the use of these known bandages the initial release will be very great, following which the release of the medicaments decreases evenly.
The adhesive layer of the bandage described in DK Patent No. 154 806 consists of a continuous water insoluble phase and a discontinuous phase which is dispersed in it and which is water soluble or water swellable, said discontinuous phase incorporating the medicament. Thus, the incorporated medicament will be released in step with the solution or swelling of liquid in the discontinuous phase, and there is thus no control of the release of the medicament.
However, a great initial release and a following declining release of the medicament can still be observed when the bandage is used on exuding wounds, and in particular if the wounds are very exuding.
Such a release profile is desired in some situations, but in other situations another release profile is desired, such as release of a constant amount of the medicament per unit of time or delayed release.
Furthermore, U.S. Pat. No. 4,904,247 describes a liquid absorbing wound bandage comprising an adhesive absorbing layer intended to face the user as well as a non-adhesive layer, wherein one of the layers or both may contain a medicament for transdermal release.
The two layers are hydrogels consisting of mixtures of hydrophilic and hydrophobic polymers, the mixture in the adhesive layer comprising at least 80% hydrophilic polymer forming a continuous matrix in which the hydrophobic polymer is dispersed.
The release of medicaments takes place by dispersion through the hydrophilic moist matrix. Thus, theoretically it is possible to obtain delayed release of the medicament by selecting an adhesive hydrogel layer without medicament. However, in practice the medicament spreads in the layers during storage, thus resulting in a release profile of the medicament which corresponds to the one obtained with the bandages mentioned above.
U.S. Pat. No. 4,781,924 discloses a bandage for release of one or more medicaments at a predetermined rate, said bandage consisting of several layers, wherein the active compound is incorporated in a first form in which it cannot be released and is changed to another form by an activating compound, which is additionally activated by water. Thus, the release from this bandage is likewise regulated by liquid action, and the release profile is substantially analogous with the release profile of the bandage known from DK Patent No. 154 806, it being possible, however, to obtain delayed release of the medicament. Thus, this bandage can only be used for quite few medicament systems and is moreover rather expensive to manufacture.
NO Published Application No. 163 438 discloses a plaster comprising a medicament reservoir which is coated with a semipermeable or perforated film membrane on the central part of the side facing the skin and is coated with an adhesive layer on the peripheral part of this side, and also the membrane may optionally be coated with adhesive. Delayed release is likewise possible with a such a plaster. However, the plaster has a very complicated structure and is thus very expensive to manufacture.
EP Patent Specification No. 144 486 discloses a bandage for transcutaneous medication and consisting of an impermeable backing layer, the reservoir layers having a medicament concentration which is above the saturation point; the medicament concentration of the layer increases from the reservoir layer facing the adhesive layer to the reservoir layer facing the backing layer.
None of these layers is mentioned as a membrane or a release controlling layer, nor is it mentioned how such a membrane effect or release controlling effect can be adjusted. If such a bandage is used directly after the manufacture, it is thus very likely, as also shown in the examples, that an increasing release of the medicament will occur and possibly also a delayed release. However, it is not mentioned how the medicament concentration differences are kept stable in the individual reservoir layers and in the adhesive layer during storage. Since the vehicle in the exemplified bandages is the same in the various layers and other components having a membrane function are not incorporated, the medicament concentration differences will be balanced completely or partly during storage, which means that the actual release profile is unpredictable when using a stored product.
Thus, such a bandage cannot be constructed to have a predetermined release profile.
EP Patent Application No. 249 343 discloses a bandage comprising a medicament reservoir and a delay layer which is interposed between the reservoir and the skin and which is impermeable to the medicament in a dry state and permeable to the medicament in a hydrated state. With this bandage it is possible to delay the initial release of the medicament. Once the release has begun, it is not possible, however, to control the rate of it.
Another type of membrane controlled transcutaneous medication bandage is mentioned in Application WO89/12470. This bandage comprises a medicament reservoir of liquid medicament, a membrane layer of an LDPE or EVE film as well as an adhesive layer which is very permeable to the medicament. With this bandage it is possible to obtain a reasonably constant release rate over a long period, but there will still be a very high initial release from the bandage. With the bandage it is not possible, however, to design other release profiles, and the bandage can moreover only be used for transcutaneous dosing of a limited number of medicaments.
EP Patent Specification 259 136 discloses a transcutaneous medication bandage comprising a layer of ethylene/vinyl acetate polymer containing the medicament in a high concentration and an adhesive layer of mineral oil/polyisobuthylene. The diffusion coefficient of the given medicament is considerably higher in the ethylene/vinyl acetate polymer layer than in the mineral oil/polyisobuthylene layer. This means that the mineral oil/polyisobuthylene layer essentially determines the release rate, and it is thus possible to obtain a bandage which has a constant release rate over a long period. However, it does not appear how this release rate can be profiled.
Thus, a large number of different mineral medication bandages are known, useful for dosing various medicaments with a delayed or constant release profile. However, most of these bandages can only be used for few medicament types. Furthermore, these bandages are very restricted with respect to the release profiles and release rates that can be obtained, and it is simultaneously a rather complicated process, which often requires many tests, to adjust or change release profiles and rates within the possible range.
The object of the present invention is to provide a dressing containing one or more medicaments and having a composition which makes it possible to design release profiles and rates within a very wide range.